Omega-3 Fatty Acids May Lower Genetic Risk for Prostate Cancer

Roxanne Nelson

June 21, 2007

June 21, 2007 — In men with a genetic predisposition to prostate cancer, the consumption of a diet rich in omega-3 fatty acids may lower the risk for disease. Results of an experimental study, published online June 21 in the Journal of Clinical Investigation, show that a diet high in omega-3 fatty acid reduced prostate tumor growth and increased survival, while omega-6 fatty acids had the opposite effects.

Increasing evidence suggests that omega-3 fatty acids, which are commonly found in fatty fish and fish oils, inhibit carcinogenesis. Specifically, write the authors, data from epidemiological studies suggest that the consumption of fish or fish oil may reduce the incidence of prostate cancer. As an example, a large prospective study of 6272 men who were followed for 30 years found that the consumption of fatty fish was associated with a lower risk for prostate cancer (Terry P et al. Lancet. 2001;357:1764–1766).

Other studies have reported significantly lower levels of omega-3 polyunsaturated fatty acids in men with benign prostate hyperplasia and prostate cancer, as compared with a control population. Conversely, levels of omega-6 fatty acids were higher in patients with prostate cancer.

The researchers point out that while the causal role of genetic alterations in human cancer has been established, the influence of environmental factors on cancer risk is still not well understood. Yong Q. Chen, PhD, a professor of cancer biology at Wake Forest University, in Winston-Salem, North Carolina, and colleagues examined the influence of both omega-3 and -6 essential fatty acids on a mouse model of prostate cancer to evaluate whether a diet rich in omega-3 polyunsaturated fatty acids can lower the incidence of cancer. The study was carried out in PTEN-knockout mice, which are bred to be predisposed to developing prostate tumors.

Overall, diets rich in omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, the researchers write. The 12-month survival rate was 60% for mice fed a diet high in omega-3, 10% on the low–omega-3 diet, and 0% on the high–omega-6 diet. The ideal ratio of omega-6 to omega-3 fatty acids is 1:1, and mice fed diets with this ratio of fatty acids were able to delay both the formation and progression of prostate tumors and prolong their survival, they comment.

The researchers also noted that animals fed a diet low in omega-3 fatty acids and with an
omega-6/omega-3 ratio of 20 (rather than a ratio of 1 in the recommended diet) had intermediary tumor growth, progression, and survival. "Therefore, the omega-6/omega-3 ratio appears to be a critical factor in the effectiveness of prostate cancer suppression, with a higher proportion of omega-3 being more effective," they write.

The introduction of the enzyme omega-3 desaturase, which is able to convert omega-6 to omega-3, reduced the growth of tumors in a fashion similar to a diet rich in omega-3 fatty acids. The investigators also found that the effect of polyunsaturated fatty acids on the development of prostate cancer is partially mediated by the protein BAD. The omega-3 fatty acids, but not omega-6, appear to induce apoptosis of prostate cancer cells through regulation of BAD.

Dr. Chen and his team also note that the absolute amount of polyunsaturated fatty acids may also play a role, as high fat intake has been associated with the risk for cancer. All of the diets initiated in this study contained 13% fat with 30% energy from fat, which is similar to the average Western diet. In control mice, normal prostate development was unaffected by the fatty-acid ratio, which suggests the importance of interactions between genes and diet and that a genetic cancer risk can be favorably modified by dietary intervention.

"Clinically, prostate cancer is usually diagnosed in men age 60 or older, and cancer cells proliferate slowly," they write. "Therefore, dietary and/or chemoprevention are of particular importance for the management of prostate cancer."

However, it has not yet been determined, they add, whether beneficial effects can also be achieved by supplementing the diet with omega-3 fatty acids in patients who have already developed the disease.

This work was supported in part by National Institutes of Health grants, the Chinese National Natural Science Foundation, and the Chang Jiang Scholars Program.

J Clin Invest. Published online June 21, 2007.



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